Over ttie past 2 decades, advances in mouse molecular genetics tiave lead to significant discoveries in neural function and development, findings that simply are not attainable without these valuable animal resources. The widespread use of genetically engineered mice has resulted in a huge array of available altered strains, which are shared widely among the research community. Additionally, the technology for generating genetically altered mice has continued to improve, and has become a conventional tool for manipulation of candidate genes. Importantly, conditional mouse genetic lines are now readily available that allow temporal and tissue specific manipulation of genes, either transiently, or indelibly. Researchers in the RMTSC employ mouse lines representing each of these aspects of cutting edge mouse molecular genetics, and in doing so, are advancing the field significantly. The primary function of Core A is to support RMTSC researcher use of mice, by maintaining breeding stocks of genetically altered mice, assisting in developing complex breeding strategies to produce offspring with the correct engineered alleles for genetic experiments, providing highly efficient genotyping of offspring, and imparting concise technical advice in the design of constructs for the genesis of new mouse lines. Given the success of our Core A in supporting mouse work through these services to RMTSC researchers in the past 9 years, the 3 overarching aims of this Core proposal remain unchanged from those ofthe previous submission. Aim 1. To maintain genetically altered mice. Aim 2. To genotype offspring of genetically altered mice.. Aim 3. To advise investigators in designing constructs for generation of genetically altered mice.